PGF2 alpha/pilocarpine interactions on IOP and accommodation in monkeys

We investigated whether (i) single or repeated topical treatment with either the tromethamine salt or the isopropyl ester of prostaglandin F2 alpha (PGF2 alpha-TS or PGF2 alpha-IE) inhibits the accommodative response to pilocarpine; (ii) pilocarpine given after PGF2 alpha inhibits the latter's ocular hypotensive effect, as occurs with the reverse order of administration. PGF2 alpha-IE (2 micrograms) or PGF2 alpha-TS (50 micrograms) was applied topically to the right eye of five cynomolgus monkeys twice daily for 4 days. Before initial dosing, and 1 hr after the initial and final dose the animals were anesthetized with ketamine, and intraocular pressure (IOP) and refraction determined bilaterally. Following post-PG IOP and refraction determinations, pilocarpine HCl was given topically (bilaterally) or infused i.m. over 10 min, after which refraction was determined periodically for 50 min. IOP was then again determined. After a single unilateral dose of PGF2 alpha-TS or PGF2 alpha-IE, IOP was unchanged. Both eyes accommodated markedly and equally in response to pilocarpine, and IOP fell bilaterally by a statistically significant 3 mmHg in response to pilocarpine. Repeated doses of PGF2 alpha-TS or PGF2 alpha-IE did not significantly affect the accommodative response to pilocarpine, while pilocarpine did not alter the approximately 10 mmHg ipsilateral IOP fall induced by repeated dosing of PGF2 alpha-TS or PGF2 alpha-IE. It is concluded that repeated unilateral topical application of PGF2 alpha-TS or PGF2 alpha-IE to the cynomolgus monkey eye markedly reduces ipsilateral IOP, but has no effect on the ipsilateral or contralateral eye accommodative response to pilocarpine. Pilocarpine reverses the PGF2 alpha-TS or PGF2 alpha-IE-induced fall in IOP when given before the PGF2 alpha, but does not prevent it when given after, within the parameters of this study.